Genetic analysis of autoimmune diseases using animal models : Mapping susceptibility genes for multiple sclerosis and rheumatoid arthritis

Sammanfattning: Autoimmune diseases such as rheumatoid arthritis and multiple sclerosis are common human diseasesaffecting 1% and 0.1% of the population respectively. These diseases are characterized by abnormal self-tolerance in the immune system and autoimmune reactions. Epidemiological studies indicate that geneticcomponents together with environmental factors influence these diseases.The etiology of autoimmune diseases is poorly understood. Previous studies have found that MHCgenes are important for disease but these studies also indicated that additional genes are involved.Studies of complex diseases such as autoimmune diseases are difficult because they are caused by more than one gene or the interactions between several genes along with environmental factors. Directanalysis of complex diseases in human families is often hampered by incomplete penetrance, phenocopies and genetic heterogeneity.Analysing complex diseases by using animal models provides a shortcut because environmental factors can be controlled and the populations are more homogenous. This thesis work has analysed several animal models for autoimmune diseases in mice and rats by genome-wide scans and multi-trait quantitative trait loci (QTL) linkage analysis. Experimental allergic encephalomyelitis (EAE) is an animal model for human MS and collagen induced arthritis (CIA) is a model for RA.We found a number of susceptiblility loci for EAE and CIA which mapped to different chromosomal regions. We mapped 3 non-MHC loci in the EAE mouse model. Also. 4 loci were mapped in the mouse CIA model and 11 loci in the EAE rat model. Among these susceptibile loci, we found that some of them are shared between EAE and arthritis and therefore may contain common autoimmune disease genes.